Published online Feb 19, 2021. doi: 10.5498/wjp.v11.i2.35
Peer-review started: October 13, 2020
First decision: December 4, 2020
Revised: December 9, 2020
Accepted: December 24, 2020
Article in press: December 24, 2020
Published online: February 19, 2021
Major depressive disorder (MDD) is a highly disabling and phenotypically heterogeneous psychiatric syndrome that is among the leading contributors to social and economic burden.
Studies from patients and animal models suggest a key role for functional imbalances between the excitatory and inhibitory neurotransmitters in the central nervous system. Somatostatin-positive (SST+) and parvalbumin-positive (PV+) neurons are two major GABAergic interneurons and play roles in excitation/inhibition balance. Type 3 adenylyl cyclase (AC3) has been reported as a top-ranked gene in MDD and our previous study indicated that AC3 globally knockout mice showed depression-like behaviors. We hope to know whether AC3 in these two subtypes of interneurons contributes to the pathophysiological process of depression.
To determine whether ablation of AC3 gene in different subtypes of GABAergic interneurons of mice produces depression-like behaviors.
Immunohistochemistry, genetic manipulations, and a series of behavior tests were used in this study.
We found that selective disruption of AC3 in SST+ but not PV+ interneurons caused anxiety- and depression-like behaviors.
AC3 in SST+ interneurons play a key role in the etiology of depression.
The AC3-dependent molecular mechanisms in SST+ interneuron underlying MDD will be further explored.